MAP4 p.Leu516=
c.1548G>A · rs142463147 · VCV714945
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.151%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.99 | GERP -3.7 |
| Overall | ||
| CADD | 1.223 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.151%
European (non-Finnish) · 1,780/1,180,038 alleles
Filtering AF
0.145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.143%
Overall
0.119%
1,927/1,614,192 alleles · rare
exomes 1,824/1,461,892 · genomes 103/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.151% | 663 |
| Finnishnot grpmax-eligible | 0.0875% | 1,143 |
| Remaining individualsnot grpmax-eligible | 0.0752% | 1,330 |
| Admixed American | 0.045% | 2,223 |
| Middle Eastern | 0.033% | 3,031 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0304% | 3,290 |
| African / African-American | 0.00799% | 12,509 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- MAP4
- Protein
- p.Leu516=
- Coding
- c.1548G>A
- MANE Select
- NM_001385682
- dbSNP
- rs142463147
- Type
- single nucleotide variant
- Location
- chr3:47916279 (GRCh38)
- Gene constraint
- LOEUF 0.512 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 43.03
- Residue 516
- the '17 x 14 aa tandem repeats' region
Similar variants
- MAP4 c.292+9T>G Benign ★★ same type
- MAP4 p.Gln1950= Benign ★★ same type
- MAP4 p.Val37= Benign ★★ same type
- MAP4 p.Ala150Ser Uncertain significance ★ ⚠ same type
- MAP4 p.Ala1922Val Uncertain significance ★ ⚠ same type
- MAP4 p.Ala1926Pro Uncertain significance ★ ⚠ same type
- MAP4 p.Ala1941Thr Uncertain significance ★ ⚠ same type
- MAP4 p.Ala1959Gly Uncertain significance ★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/map4-p-leu516 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown